{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:26:54Z","timestamp":1779100014506,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian Research Foundation","award":["NKFI K138871"],"award-info":[{"award-number":["NKFI K138871"]}]},{"name":"Hungarian Research Foundation","award":["TKP2021-EGA"],"award-info":[{"award-number":["TKP2021-EGA"]}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["NKFI K138871"],"award-info":[{"award-number":["NKFI K138871"]}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021-EGA"],"award-info":[{"award-number":["TKP2021-EGA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared through the methyl ester of the allilyc diol derived from steviol. The oxirane ring was opened with primary and secondary amines, providing a versatile library of aminotriols. The corresponding primary aminotriol was formed by palladium-catalysed hydrogenation, and an N,O-heterocyclic compound was synthesised in a regioselective reaction. All new compounds were characterised by 1D- and 2D-NMR techniques and HRMS measurements. In our in vitro investigations, we found that the aromatic N-substituted derivatives exhibited high inhibition of cell growth on human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). The antiproliferative activities were assayed by the MTT method. Furthermore, the introduction of an additional hydroxy group slightly increased the biological activity. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.<\/jats:p>","DOI":"10.3390\/ijms24021121","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T01:36:17Z","timestamp":1673228177000},"page":"1121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Stereoselective Synthesis and Antiproliferative Activities of Tetrafunctional Diterpene Steviol Derivatives"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-4070","authenticated-orcid":false,"given":"Dorottya","family":"Bai","sequence":"first","affiliation":[{"name":"Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8519-4830","authenticated-orcid":false,"given":"Zsuzsanna","family":"Schelz","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f3ra","family":"Erd\u0151s","sequence":"additional","affiliation":[{"name":"Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Muegyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3743-0958","authenticated-orcid":false,"given":"Anna K.","family":"Kis","sequence":"additional","affiliation":[{"name":"Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Muegyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikt\u00f3ria","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-5300","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Zupk\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Natural Products, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gy\u00f6rgy T.","family":"Balogh","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"},{"name":"Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Muegyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-8409","authenticated-orcid":false,"given":"Zsolt","family":"Szakonyi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Natural Products, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hawash, M. 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